tbuckley/cabot-search huggingface dataset:
In adults with obesity without diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk
Authors: Mayer B. Davidson
Journal: Annals of Internal Medicine (2022)

ACP Journal ClubOctober 2022In adults with obesity without diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wkMayer B. Davidson, MDMayer B. Davidson, MDCharles R. Drew University, Los Angeles, California, USA (M.B.D.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/J22-0072 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationJastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-16. https://pubmed.ncbi.nlm.nih.gov/35658024Clinical Impact RatingsGIM/FP/GP: Endocrinology: References1. US Preventive Services Task Force; Curry SJ, Krist AH, et al. Behavioral weight loss interventions to prevent obesity-related morbidity and mortality in adults: US Preventive Services Task Force recommendation statement. JAMA. 2018;320:1163-71. [PMID: 30326502] Google Scholar2. Aroda VR. A review of GLP-1 receptor agonists: evolution and advancements, through the lens of randomised controlled trials. Diabetes Obes Metab. 2018;20 Suppl 1:22-33. [PMID: 29364586] Google Scholar3. Wilding JP, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384:989-1002. [PMID: 33567185] Google Scholar4. Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the Step 4 randomized clinical trial. JAMA. 2021;325:1414-25. [PMID: 33755728] Google Scholar5. Samms RJ, Coghlan MP, Sloop KW. How may GIP enhance the therapeutic efficacy of GLP-1? Trends Endocrinol Metab. 2020;31:410-21. [PMID: 32396843] Google Scholar Author, Article, and Disclosure InformationAffiliations: Charles R. Drew University, Los Angeles, California, USA (M.B.D.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J22-0072.This article was published at Annals.org on 4 October 2022.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTirzepatide: A Systematic Update October 2022Volume 175, Issue 10Page: JC116KeywordsBody mass indexBody weightDrugsEatingObesityOverweightPeptide hormonesSurgeryWeight loss ePublished: 4 October 2022 Issue Published: October 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Impediments to Heart Transplantation in Adults With MELAS:m.3243A&gt;G Cardiomyopathy
Authors: Alessandro Di Toro, Mario Urtis, Nupoor Narula, Lorenzo Giuliani, Maurizia Grasso, Michele Pasotti, Carlo Pellegrini, Alessandra Serio, Andrea Pilotto, Elena Antoniazzi, Teresa Rampino, Lorenzo Magrassi, Adele Valentini, Anna Cavallini, Laura Scelsi, Stefano Ghio, Massimo Abelli, Iacopo Olivotto, Maurizio Porcu, Antonello Gavazzi, Takahide Kodama, Eloisa Arbustini
Journal: Journal of the American College of Cardiology (2022)

The heart is commonly involved in maternally inherited mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome caused by the MT-TL1 m.3243A>G mutation of the mitochondrial DNA. Heart transplantation (HTx) is controversial and has rarely been performed with conflicting results. We analyzed factors preventing HTx in consecutive adult patients with MELASMT-TL1:m.3243A>G cardiomyopathy diagnosed and followed during the last 23 years in our HTx referral center. The series consists of 14 unrelated adult probands who were referred for evaluation of cardiomyopathy from 1998 to 2021. None had a suspected diagnosis of MELAS before referral. All patients underwent clinical and genetic visit and counseling, mitochondrial DNA sequencing, cardiovascular investigation (including right heart catheterization and endomyocardial biopsy in 10), multidisciplinary assessment, and biochemical tests. Family screening identified 2 affected relatives. The cardiac phenotype was characterized by hypertrophic, concentric, nonobstructive cardiomyopathy that often evolved into a dilated cardiomyopathy-like phenotype. Of the 14 probands, 7 were potential candidates for HTx, 2 for heart and kidney Tx, and 1 was on the active HTx list for 3 years. None of the 10 probands underwent HTx. One is currently being evaluated for HTx. All had diabetes, hearing loss, and myopathy, and 10 had chronic kidney disease and progressive encephalomyopathy. During follow-up, 10 died from heart failure associated with multiorgan failure within 5 years of the genetic diagnosis. High risk of stroke-like episodes, chronic kidney disease, and wasting myopathy in MELASMT-TL1:m.3243A>G patients prevents activation of plans for HTx. As a result, the management of their cardiomyopathy in this syndromic context remains an unmet clinical need.
Cardiac Phenotypes in Secondary Hypertension
Authors: Andrzej Januszewicz, Paolo Mulatero, Piotr Dobrowolski, Silvia Monticone, Patricia Van der Niepen, Pantelis Sarafidis, Martin Reincke, Emrush Rexhaj, Graeme Eisenhofer, Magdalena Januszewicz, Alexandros Kasiakogias, Reinhold Kreutz, Jacques W.M. Lenders, Maria Lorenza Muiesan, Alexandre Persu, Enrico Agabiti-Rosei, Rodrigo Soria, Mateusz Śpiewak, Aleksander Prejbisz, Franz H. Messerli
Journal: Journal of the American College of Cardiology (2022)

Several forms of secondary hypertension carry a high risk of cardiac morbidity and mortality. Evaluation of cardiac phenotypes in secondary hypertension provides a unique opportunity to study underlying hormonal and biochemical mechanisms affecting the heart. We review the characteristics of cardiac dysfunction in different forms of secondary hypertension and clarify the mechanisms behind the higher prevalence of heart damage in these patients than in those with primary hypertension. Attention to the specific clinical/biochemical phenotypes of these conditions may assist clinicians to screen for and confirm secondary forms of hypertension. Thereby, early signs of heart damage can be recognized and monitored, allowing individualized treatment to delay or prevent evolution toward more advanced disease.
Heterogeneity in Obesity Prevalence Among Asian American Adults
Authors: Nilay S. Shah, Cecily Luncheon, Namratha R. Kandula, Sadiya S. Khan, Liping Pan, Cathleen Gillespie, Fleetwood Loustalot, Jing Fang
Journal: Annals of Internal Medicine (2022)

Background: Obesity increases the risk for metabolic and cardiovascular disease, and this risk occurs at lower body mass index (BMI) thresholds in Asian adults than in White adults. The degree to which obesity prevalence varies across heterogeneous Asian American subgroups is unclear because most obesity estimates combine all Asian Americans into a single group. Objective: To quantify obesity prevalence in Asian American subgroups among U.S. adults using both standard BMI categorizations and categorizations tailored to Asian populations. Design: Cross-sectional. Setting: United States, 2013 to 2020. Participants: The analytic sample included 2 882 158 adults aged 18 years or older in the U.S. Behavioral Risk Factor Surveillance System surveys (2013 to 2020). Participants self-identified as non-Hispanic White ([NHW] n = 2 547 965); non-Hispanic Black ([NHB] n = 263 136); or non-Hispanic Asian ([NHA] n = 71 057), comprising Asian Indian (n = 13 916), Chinese (n = 11 686), Filipino (n = 11 815), Japanese (n = 12 473), Korean (n = 3634), and Vietnamese (n = 2618) Americans. Measurements: Obesity prevalence adjusted for age and sex calculated using both standard BMI thresholds (≥30 kg/m2) and BMI thresholds modified for Asian adults (≥27.5 kg/m2), based on self-reported height and weight. Results: Adjusted obesity prevalence (by standard categorization) was 11.7% (95% CI, 11.2% to 12.2%) in NHA, 39.7% (CI, 39.4% to 40.1%) in NHB, and 29.4% (CI, 29.3% to 29.5%) in NHW participants; the prevalence was 16.8% (CI, 15.2% to 18.5%) in Filipino, 15.3% (CI, 13.2% to 17.5%) in Japanese, 11.2% (CI, 10.2% to 12.2%) in Asian Indian, 8.5% (CI, 6.8% to 10.5%) in Korean, 6.5% (CI, 5.5% to 7.5%) in Chinese, and 6.3% (CI, 5.1% to 7.8%) in Vietnamese Americans. The prevalence using modified criteria (BMI ≥27.5 kg/m2) was 22.4% (CI, 21.8% to 23.1%) in NHA participants overall and 28.7% (CI, 26.8% to 30.7%) in Filipino, 26.7% (CI, 24.1% to 29.5%) in Japanese, 22.4% (CI, 21.1% to 23.7%) in Asian Indian, 17.4% (CI, 15.2% to 19.8%) in Korean, 13.6% (CI, 11.7% to 15.9%) in Vietnamese, and 13.2% (CI, 12.0% to 14.5%) in Chinese Americans. Limitation: Body mass index estimates rely on self-reported data. Conclusion: Substantial heterogeneity in obesity prevalence exists among Asian American subgroups in the United States. Future studies and public health efforts should consider this heterogeneity. Primary Funding Source: National Heart, Lung, and Blood Institute.
CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment
Authors: Zongfu Pan, Tong Xu, Lisha Bao, Xiaoping Hu, Tiefeng Jin, Jinming Chen, Jianqiang Chen, Yangyang Qian, Xixuan Lu, Lu li, Guowan Zheng, Yiwen Zhang, Xiaozhou Zou, Feifeng Song, Chuanming Zheng, Liehao Jiang, Jiafeng Wang, Zhuo Tan, Ping Huang, Minghua Ge
Journal: Molecular Cancer (2022)

Abstract Anaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription - factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression - free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single - cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha - smooth muscle actin (α - SMA) - positive cancer - associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α - SMA - positive CAFs through CREB3L1 - mediated IL - 1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF - like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC. Graphical Abstract
H3K18 lactylation marks tissue-specific active enhancers
Authors: Eva Galle, Chee-Wai Wong, Adhideb Ghosh, Thibaut Desgeorges, Kate Melrose, Laura C. Hinte, Daniel Castellano-Castillo, Magdalena Engl, Joao Agostinho de Sousa, Francisco Javier Ruiz-Ojeda, Katrien De Bock, Jonatan R. Ruiz, Ferdinand von Meyenn
Journal: Genome biology (2022)
Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases
Authors: Gregory Heller, Allison M. Bradbury, Mark S. Sands, Ernesto R. Bongarzone
Journal: Molecular Therapy (2022)

Krabbe disease (KD) is a lysosomal storage disease (LSD) caused by mutations in the galc gene. There are over 50 monogenetic LSDs, which largely impede the normal development of children and often lead to premature death. At present, there are no cures for LSDs and the available treatments are generally insufficient, short acting, and not without co-morbidities or long-term side effects. The last 30 years have seen significant advances in our understanding of LSD pathology as well as treatment options. Two gene therapy-based clinical trials, NCT04693598 and NCT04771416, for KD were recently started based on those advances. This review will discuss how our knowledge of KD got to where it is today, focusing on preclinical investigations, and how what was discovered may prove beneficial for the treatment of other LSDs.
A bioactive glass functional hydrogel enhances bone augmentation via synergistic angiogenesis, self-swelling and osteogenesis
Authors: Fujian Zhao, Zhen Yang, Huacui Xiong, Yang Yan, Xiaofeng Chen, Longquan Shao
Journal: Bioactive Materials (2022)

Bone augmentation materials usually cannot provide enough new bone for dental implants due to the material degradation and mucosal pressure. The use of hydrogels with self-swelling properties may provide a higher bone augmentation, although swelling is generally considered to be a disadvantage in tissue engineering. Herein, a double-crosslinked gelatin-hyaluronic acid hydrogels (GH) with self-swelling properties were utilized. Meanwhile, niobium doped bioactive glasses (NbBG) was dispersed in the hydrogel network to prepare the GH-NbBG hydrogel. The composite hydrogel exhibited excellent biocompatibility and the addition of NbBG significantly improved the mechanical properties of the hydrogel. In vivo results found that GH-NbBG synergistically promoted angiogenesis and increased bone augmentation by self-swelling at the early stage of implantation. In addition, at the late stage after implantation, GH-NbBG significantly promoted new bone formation by activating RUNX2/Bglap signaling pathway. Therefore, this study reverses the self-swelling disadvantage of hydrogels into advantage and provides novel ideas for the application of hydrogels in bone augmentation.
Front Cover Image, Volume 42, Issue 6
Authors: Luana Xavier Soares Gomes Moura Fé, Eliane Pereira Cipolatti, Martina Costa Cerqueira Pinto, Suema Branco, Fábio César Sousa Nogueira, Gisela Maria Dellamora Ortiz, Anderson de Sá Pinheiro, Evelin Andrade Manoel
Journal: Medicinal Research Reviews (2022)
Current Medical Literature
Journal: JAMA (1906)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Highlights of This Issue
Journal: Clinical Cancer Research (2012)

Mehta and colleagues examined the immunomodulatory effects and antitumor activity of letrozole when combined with L-BLP25 in the human MUC1-expressing mammary tumor mouse model. L-BLP25 is currently the most advanced MUC1-specific liposomal vaccine in clinical development. The majority of breast cancers overexpress the MUC1 glycoprotein, making MUC1 a logical target for immunotherapy. The aromatase inhibitor letrozole, when combined with L-BLP25, showed a significant survival benefit. This is the first evidence that immunotherapy combined with hormonal therapy has efficacy in a breast cancer mouse model. The present study supports clinical development of L-BLP25 immunotherapy combined with letrozole as a potential new treatment and prevention strategy for breast cancer.Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. Merkel cell polyomavirus (MCPyV) DNA is found in approximately 70% of MCCs, and in such tumors MCPyV infection likely has a role in tumorigenesis. Sihto and colleagues found that high numbers of T cells, macrophages, and natural killer cells were associated with presence of MCPyV DNA in MCC, but patients with high tumor T-cell counts turned out to have favorable survival regardless of whether cancer contained MCPyV DNA or not. This finding suggests that host immune defense influences MCC patient outcome irrespective of the tumor MCPyV infection status.To identify DNA methylation biomarkers for diagnosis, prediction of recurrence, clinical recurrence, and systematic progression of prostate cancer, Mahapatra and colleagues profiled the methylation of 14,495 genes in 238 prostate cancer tissues. The sensitivity and specificity of methylation for 25 genes from tumor versus matched normal, recurrence versus nonrecurrence, systemic recurrence versus local recurrence, and 7 genes from clinical recurrence versus biochemical recurrence groups were shown. Validation of the selected genes from the different groups confirmed the microarray results. This study shows the significance of genes as diagnostic and prognostic biomarkers of prostate cancer.A large percentage of patients with pancreatic cancer (80%) have concurrent diabetes or impaired glucose tolerance. To explore whether use of the antidiabetic drug metformin, a promising antitumor agent, affects the clinical outcome of pancreatic cancer, Sadeghi and colleagues conducted a retrospective study in 302 diabetic patients with pancreatic cancer. The authors observed that overall survival time was 4 months longer in metformin users, with a 32% reduced risk of death and 2-fold higher 2-year survival rate than those in the control group. This finding should prompt future research to test the hypothesis that metformin can be used as a supplemental therapy in the treatment of pancreatic cancer.
Predicting outcome for stroke, TIA patients
Authors: William A. Check
Journal: JAMA (1982)

Progress in estimating the probability of recovery of stroke victims on the basis of their clinical status has been reported by a group of neurologists from Cornell University Medical College, New York City. Not all patients or their families want to know the likelihood of regaining normal function after an ischemic attack, concedes David Levy, MD. Still, he told<i>JAMA</i>MEDICAL NEWS, "Patients' families ask me all the time to estimate whether their relative will recover from a stroke. They need such information to make financial decisions and to prepare for the future care of the person." Such decisions already are made everyday by rehabilitation centers, Levy pointed out, "but right now they are not made on the basis of facts. There is just no accurate information available to clinicians on which to predict recovery from stroke." The study group was composed of 107 patients seen at the hospital within
Quantitative detection of hepatitis C virus RNA with a solid-phase signal amplification method: Definition of optimal conditions for specimen collection and clinical application in interferon-treated patients
Authors: Gary L. Davis, Johnson Y.-N. Lau, Mickie S. Urdea, Paul D. Neuwald, Judith C. Wilber, Karen Lindsay, Robert P. Perrillo, Janice Albrecht
Journal: Hepatology (1994)

To determine the optimal conditions for preparation of serum specimens for quantitative hepatitis C virus RNA determination, patient samples were processed such that differences in time from clot formation to centrifugation, centrifugation to separation of serum and collection of serum until freezing could be independently assessed. The effects of multiple cycles of freezing and thawing were also determined. There was progressive and significant loss of hepatitis C virus RNA activity when the time from the formation of the clot until centrifugation was longer than 2 hr. This reduction reached 32% after 6 hr and 49% after 24 hr. If centrifugation was performed immediately after formation of the clot, loss of hepatitis C virus RNA activity was reduced to less than 10% even though the serum remained unseparated from the clot for up to 6 hr. Centrifugation of blood through a paraffin plug (serum separator tube) prevented loss of hepatitis C virus RNA activity for up to 24 hr. There was no loss of hepatitis C virus RNA activity with up to three freeze-thaw cycles. When patient specimens were prepared under these optimal conditions, the sensitivity of the quantitative branched DNA signal amplification assay in patients with hepatitis C virus infection was 83% and the specificity in patients with liver disease was 100%. Fluctuations in hepatitis C virus RNA levels were shown to correlate with biochemical changes observed in patients treated with recombinant inter-feron-α 2b . These data demonstrate that improper or inconsistent methods of serum preparation may result in falsely low and unreliable levels of hepatitis C virus RNA. Clinical applications of quantitative hepatitis C virus RNA assays will only be possible when sera are properly prepared. (Hepatology 1994;19:1337-1341.)
Development of Virus-Accelerated Thymic Lymphoma in AKR Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Journal: JNCI Journal of the National Cancer Institute (1985)

The progression of prelymphoma cells (PLC) in the bone marrow to lymphoma cells (LC) in the thymus in the presence of the lymphomagenic retrovirus SL3-3C was studied in a model system of virus-accelerated thymic lymphoma in AKR/J mice. On the average, a single LC appears in the thymus 30 days after the neonatal ip inoculation of SL3-3C virus; 50 days later, thymic lymphoma is clinically detectable. PLC in the bone marrow and oncogenic virus in the thymus are continuously present during this period before lymphoma develops. Biologically active oncogenic virus in the thymus increases as the animal nears the time of lymphoma development. Intrathymic inoculation, but not ip inoculation, of SL3-3C virus results in accelerated thymic lymphoma in 4-to 6-week-old AKR mice. PLC defined as a population of bone marrow-derived thymocyte progenitor cells susceptible to malignant transformation by oncogenic retrovirus after homing to thymus were further studied and characterized. PLC, like normal bone marrow thymocyte progenitors, were found to be radiosensitive and glucocorticoid resistant. Thymocytes of 21- to 28-day-old AKR mice, neonatally inoculated with SL3-3C virus, were studied for PLC. They could not be detected. It is concluded that lymphoma development is the final outcome of a series of events in which bone marrow-derived thymocyte progenitors are transformed after entering the thymus by virus in the thymic environment.